Multi-tasking protein has potential to protect against disease

Wednesday, May 17, 2023

By Jon Atherton

Our bodies reproduce trillions of new cells in order to grow and develop. But when our DNA divides unevenly, stress in our cells can lead to diseases such as cancer. The separation of our DNA into new cells – a process called mitosis - is carefully controlled and protected by certain proteins that scientists have yet to fully understand.

Work at the Yale Cancer Biology Institute (YCBI) has uncovered a new and important role for a protein previously thought to perform just one task – to protect cells only by responding to DNA damage and cell stress.

Instead, the scientists found that the protein – called ATR – also plays an important role as a protector of genome stability. Published in Cell Reports, the findings change the way we think about ATR’s function and the importance of DNA composition for cellular processes.

“We’re trying to understand the mechanisms that protect against uneven cell division,” said Lillian Kabeche, assistant professor in the department of Molecular Biophysics and Biochemistry, member of the YCBI, and senior author of the study.

“When we identify all the ways a protein works, we can better predict how drugs targeting that protein will affect patients.”

ATR protein is currently targeted by inhibitor therapies in cancer treatment, but the scientists hope to explore new therapeutic targets that also work to protect healthy cells, for example to prevent the side effects of chemotherapy.

Lab experiments were led by graduate student Isabelle Trier, who was first author of the study. Additional authors from the Kabeche Lab were Elizabeth Black and Yoon Ki Joo. The work is supported by a Pershing Square Sohn Award.